The proposed experiments in animals (dogs) are designed to provide solutions to the following problems that presently prevent lung transplantation from being practical therapeutically: 1. How may the functional defects of lung allograft rejection be prevented or reversed safely? To this end, we must first understand better the mechanisms which produce lung rejection. We will, therefore, continue immunofluorescent studies to identify the mediators of rejection so they can be more safely and effectively blocked. We will also use in vivo microscopy, radioactive particles, and electron microscopy to identify the nature of early rejection damage in the lung so that it can be better prevented. We will also study the mechanism whereby methylprednisolone dramatically reverses manifestations of lung rejection and the efficacy of tolerance and enhancement in preventing lung rejection. 2. How may lung rejection be identified earlier, more accurately and more safely? For this, we will study a) transbronchial lung biopsy, b) lavage sampling of alveolar material with and without tracer substances, and c) various immunologic methods. Early accurate detection of rejection will facilitate its prevention or reversal. 3. What is the optimal unit of lung tissue for transplantation? To resolve this, we will perform autografts and allografts in dogs with experimental emphysema. 4. What is the cause of bronchial anastomotic problems and how may they be minimized? We will study this problem by endoscopic, morphologic, and angiographic evaluation of bronchial anastomoses under various conditions. 5. How may the supply of donor lungs be increased? In an attempt to solve this problem, we will continue our studies in lung preservation and lung xenografting.